Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Tracking the carbons supplying gluconeogenesis.

ABSTRACT: As the burden of type 2 diabetes mellitus (T2DM) grows in the 21st century, the need to understand glucose metabolism heightens. Increased gluconeogenesis is a major contributor to the hyperglycemia seen in T2DM. Isotope tracer experiments in humans and animals over several decades have offered insights into gluconeogenesis under euglycemic and diabetic conditions. This review focuses on the current understanding of carbon flux in gluconeogenesis, including substrate contribution of various gluconeogenic precursors to glucose production. Alterations of gluconeogenic metabolites and fluxes in T2DM are discussed. We also highlight ongoing knowledge gaps in the literature that require further investigation. A comprehensive analysis of gluconeogenesis may enable a better understanding of T2DM pathophysiology and identification of novel targets for treating hyperglycemia.

SUBMITTER: Shah AM

PROVIDER: S-EPMC7573258 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Tracking the carbons supplying gluconeogenesis.

Shah Ankit M AM Wondisford Fredric E FE

The Journal of biological chemistry 20200813 42

As the burden of type 2 diabetes mellitus (T2DM) grows in the 21st century, the need to understand glucose metabolism heightens. Increased gluconeogenesis is a major contributor to the hyperglycemia seen in T2DM. Isotope tracer experiments in humans and animals over several decades have offered insights into gluconeogenesis under euglycemic and diabetic conditions. This review focuses on the current understanding of carbon flux in gluconeogenesis, including substrate contribution of various gluc ...[more]

PMID: 32817317

Similar Datasets

Electrochemical metallization cell with anion supplying active electrode.

Project description:Electrochemical metallization (ECM) memories are among the various emerging non-volatile memory technologies, contending to replace DRAM and Flash and enabling novel neuromorphic computing applications. Typically, the operation of ECM cell is based on the electrochemical redox reactions of the cation supplying active electrode (e.g., Ag, Cu). Although extensively investigated, the possibility of utilizing new materials for the active electrode remains largely undiscussed. In this paper, an ECM cell with a Te active electrode is fabricated. It is found that the SET operation of the device occurs under negative voltage on the active electrode, which is opposite to that of the device with Ag electrode, indicating that the Te electrode supplies Te2- anions by electrochemical reduction. The influence of the electrolyte material on the switching properties is also found to be more significant for devices with Te electrodes. For Pt/GeS/Te and Pt/Ge2Sb2Te5/Te cells, repeatable unipolar and bipolar resistive switching are observed, respectively, which can be attributed to the rupture of the filament by Joule heating for the former and by ECM for the latter in the RESET process. The semiconducting properties of Te, the reversed operating polarity and the electrolyte dependent switching characteristics open up unprecedented prospects for ECM cells.

| S-EPMC6105648 | biostudies-literature

Nutrient-supplying ocean currents modulate coral bleaching susceptibility.

Project description:With predictions that mass coral bleaching will occur annually within this century, conservation efforts must focus their limited resources based on an accurate understanding of the drivers of bleaching. Here, we provide spatial and temporal evidence that excess nutrients exacerbate the detrimental effects of heat stress to spark mass coral bleaching in the Red Sea. Exploiting this region's unique oceanographic regime, where nutrients and heat stress vary independently, we demonstrate that the world's third largest coral reef system historically suffered from severe mass bleaching only when exposed to both unusually high temperature and nutrients. Incorporating nutrient-supplying ocean currents and their variability into coral bleaching forecasts will be critical for effectively guiding efforts to safeguard the reefs most likely to persist in the Anthropocene.

| S-EPMC7442482 | biostudies-literature

Silicoaluminophosphate (SAPO)-Templated Activated Carbons.

Project description:Microporous activated carbon was prepared by depositing and pyrolyzing propylene within the microporous voids of SAPO-37 and subsequently removing the template by a treatment with HCl and NaOH. The carbon had a high surface area and large micropore and ultramicropore volumes. The yield, crystallinity, morphology, and adsorption properties compared well with those of a structurally related zeolite-Y-templated carbon. No HF was needed to remove the SAPO-37 template in contrast to the zeolite Y template, which could be of industrial importance.

| S-EPMC6648489 | biostudies-literature

Do hospitals respond to decreasing prices by supplying more services?

Project description:Regulated prices are common in markets for medical care. We estimate the effect of changes in regulated reimbursement prices on volume of hospital care based on a reform of hospital financing in Germany. Uniquely, this reform changed the overall level of reimbursement-with increasing prices for some hospitals and decreasing prices for others-without directly affecting the relative prices for different groups of patients or types of treatment. Based on administrative data, we find that hospitals react to increasing prices by decreasing the service supply and to decreasing prices by increasing the service supply. Moreover, we find some evidence that volume changes for hospitals with different price changes are nonlinear. We interpret our findings as evidence for a negative income effect of prices on volume of care.

| S-EPMC7004180 | biostudies-literature

Fast Microwave Synthesis of Hierarchical Porous Carbons from Waste Palm Boosted by Activated Carbons for Supercapacitors.

Project description:The synthesis of biomass-derived porous carbons (PCs) for supercapacitors by conventional two-steps method (chemical activation after carbonization) is complicated and time-consuming. In this study, we present a one-step microwave activation strategy to prepare hierarchically PCs from waste palm boosted by activated carbons (ACs). ACs with various specific surface areas (14, 642, and 1344 m²·g-1) were used for the first time to fast absorb microwave energy for converting waste palm into hierarchically PCs, that is, PC1, PC2, and PC3, respectively. The morphological and structural characterizations of PCs were studied. Also, the electrochemical performances of supercapacitors based on PCs as electrodes were further investigated. The results showed that the PC (PC1) boosted by AC with the lowest specific surface area possessed a porous structure (containing micro-, meso-, and macro- pores) with the largest specific surface area (1573 m²·g-1) and the highest micropore volume (0.573 cm³·g-1), as well as the suitable mesoporosity (29.69%). The as-prepared PC1 supercapacitor even in a gel electrolyte (PVA/LiCl) exhibited a high specific capacitance of 226.0 F·g-1 at 0.5 A·g-1 and presented excellent charge-discharge performance with an energy density of 72.3 Wh·kg-1 at a power density of 1.4 kW·kg-1 and 50.0 Wh·kg-1 at 28.8 kW·kg-1. Moreover, this promising method exhibited a simple, rapid, and cost-effective preparation of carbon materials from renewable biomass for energy storage applications.

| S-EPMC6473988 | biostudies-literature

Supplying a pharmacy for NASA exploration spaceflight: challenges and current understanding.

Project description:In order to maintain crew health and performance during long-duration spaceflight outside of low-Earth orbit, NASA and its international partners must be capable of providing a safe and effective pharmacy. Given few directed studies of pharmaceuticals in the space environment, it is difficult to characterize pharmaceutical effectiveness or stability during spaceflight; this in turn makes it challenging to select an appropriate formulary for exploration. Here, we present the current state of literature regarding pharmaceutical stability, metabolism, and effectiveness during spaceflight. In particular, we have attempted to highlight the gaps in current knowledge and the difficulties in translating terrestrial-based drug studies to a meaningful interpretation of drug stability, safety, and effectiveness in space. We hope to identify high-yield opportunities for future research that might better define and mitigate pharmaceutical risk for exploration missions.

| S-EPMC6565689 | biostudies-literature

Control of hepatic gluconeogenesis by Argonaute2.

Project description:ObjectiveThe liver performs a central role in regulating energy homeostasis by increasing glucose output during fasting. Recent studies on Argonaute2 (Ago2), a key RNA-binding protein mediating the microRNA pathway, have illustrated its role in adaptive mechanisms according to changes in metabolic demand. Here we sought to characterize the functional role of Ago2 in the liver in the maintenance of systemic glucose homeostasis.MethodsWe first analyzed Ago2 expression in mouse primary hepatocyte cultures after modulating extracellular glucose concentrations and in the presence of activators or inhibitors of glucokinase activity. We then characterized a conditional loss-of-function mouse model of Ago2 in liver for alterations in systemic energy metabolism.ResultsHere we show that Ago2 expression in liver is directly correlated to extracellular glucose concentrations and that modulating glucokinase activity is adequate to affect hepatic Ago2 levels. Conditional deletion of Ago2 in liver resulted in decreased fasting glucose levels in addition to reducing hepatic glucose production. Moreover, loss of Ago2 promoted hepatic expression of AMP-activated protein kinase α1 (AMPKα1) by de-repressing its targeting by miR-148a, an abundant microRNA in the liver. Deletion of Ago2 from hyperglycemic, obese, and insulin-resistant Lepob/ob mice reduced both random and fasted blood glucose levels and body weight and improved insulin sensitivity.ConclusionsThese data illustrate a central role for Ago2 in the adaptive response of the liver to fasting. Ago2 mediates the suppression of AMPKα1 by miR-148a, thereby identifying a regulatory link between non-coding RNAs and a key stress regulator in the hepatocyte.

| S-EPMC6308973 | biostudies-literature

Sam68 promotes hepatic gluconeogenesis via CRTC2.

Project description:Hepatic gluconeogenesis is essential for glucose homeostasis and also a therapeutic target for type 2 diabetes, but its mechanism is incompletely understood. Here, we report that Sam68, an RNA-binding adaptor protein and Src kinase substrate, is a novel regulator of hepatic gluconeogenesis. Both global and hepatic deletions of Sam68 significantly reduce blood glucose levels and the glucagon-induced expression of gluconeogenic genes. Protein, but not mRNA, levels of CRTC2, a crucial transcriptional regulator of gluconeogenesis, are >50% lower in Sam68-deficient hepatocytes than in wild-type hepatocytes. Sam68 interacts with CRTC2 and reduces CRTC2 ubiquitination. However, truncated mutants of Sam68 that lack the C- (Sam68ΔC) or N-terminal (Sam68ΔN) domains fails to bind CRTC2 or to stabilize CRTC2 protein, respectively, and transgenic Sam68ΔN mice recapitulate the blood-glucose and gluconeogenesis profile of Sam68-deficient mice. Hepatic Sam68 expression is also upregulated in patients with diabetes and in two diabetic mouse models, while hepatocyte-specific Sam68 deficiencies alleviate diabetic hyperglycemia and improves insulin sensitivity in mice. Thus, our results identify a role for Sam68 in hepatic gluconeogenesis, and Sam68 may represent a therapeutic target for diabetes.

| S-EPMC8185084 | biostudies-literature

Glucagon changes substrate preference in gluconeogenesis.

Project description:Fasting hyperglycemia in diabetes mellitus is caused by unregulated glucagon secretion that activates gluconeogenesis (GNG) and increases the use of pyruvate, lactate, amino acids, and glycerol. Studies of GNG in hepatocytes, however, tend to test a limited number of substrates at nonphysiologic concentrations. Therefore, we treated cultured primary hepatocytes with three identical substrate mixtures of pyruvate/lactate, glutamine, and glycerol at serum fasting concentrations, where a different U-13C- or 2-13C-labeled substrate was substituted in each mix. In the absence of glucagon stimulation, 80% of the glucose produced in primary hepatocytes incorporated either one or two 13C-labeled glycerol molecules in a 1:1 ratio, reflecting the high overall activity of this pathway. In contrast, glucose produced from 13C-labeled pyruvate/lactate or glutamine rarely incorporated two labeled molecules. While glucagon increased the glycerol and pyruvate/lactate contributions to glucose carbon by 1.6- and 1.8-fold, respectively, the glutamine contribution to glucose carbon was increased 6.4-fold in primary hepatocytes. To account for substrate 13C carbon loss during metabolism, we also performed a metabolic flux analysis, which confirmed that the majority of glucose carbon produced by primary hepatocytes was from glycerol. In vivo studies using a PKA-activation mouse model that represents elevated glucagon activity confirmed that most circulating lactate carbons originated from glycerol, but very little glycerol was derived from lactate carbons, reflecting glycerol's importance as a carbon donor to GNG. Given the diverse entry points for GNG substrates, hepatic glucagon action is unlikely to be due to a single mechanism.

| S-EPMC9747632 | biostudies-literature

Activated Carbons from Hydrochars Prepared in Milk.

Project description:Hydrothermal carbonization converts organics in aqueous suspension to a mixture of liquid components and carbon-rich solids (hydrochars), which in turn can be processed into activated carbons. We investigated whether milk could be used as a medium for hydrothermal carbonization, and found that hydrochars prepared from milk, with or without an added fibrous biomass, contained more carbon (particularly aliphatic carbon), less oxygen, and more mineral components than those prepared from fibrous biomass in water. Activated carbons produced from hydrochars generated in milk had lower specific surface areas and CO2 capacities than those from hydrochars formed in water; however, these differences disappeared upon normalizing to the combustible mass of the solid. Thus, in the context of N2 and CO2 uptake on activated carbons, the primary effect of using milk rather than water to form the hydrochar precursor was to contribute inorganic mass that adsorbed little CO2. Nevertheless, some of the activated carbons generated from hydrochars formed in milk had specific CO2 uptake capacities in the normal range for activated carbons prepared by activation in CO2 (here, up to 1.6 mmol g-1 CO2 at 15 kPa and 0 °C). Thus, hydrothermal carbonization could be used to convert waste milk to hydrochars and activated carbons.

| S-EPMC6861549 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data